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Coumadin



Warfarin (also known under the brand names of Coumadin and Marevan) is an anticoagulant medication that is administered orally. It is used for the prophylaxis of thrombosis and embolism in many disorders. Its activity has to be monitored by frequent blood testing for the international normalized ratio (INR). It is named for the Wisconsin Alumni Research Foundation.


Warfarin was originally developed as a rat poison, and is still widely used as such, although warfarin-resistant rats are becoming more common.

Coumadin Drug
Mechanism of action
Warfarin inhibits the synthesis of biologically active forms of the Vitamin K dependent clotting factors: II, VII, IX and X, as well as the regulatory factors protein C and protein S.

The precursors of these factors require carboxylation of their glutamic acid residues to become biologically competent. This carboxylation is linked to oxidation of Vitamin K to form Vitamin K epoxide, which is in turn recycled back to the reduced form by the enzyme epoxide reductase. Warfarin inhibits epoxide reductase, thereby inhibiting production of coagulation factors. As the body stores of previously-produced factors degrade (over several days), the anticoagulation effect becomes apparent.

Uses

Medical use
Warfarin is given to people with an excessive tendency for thrombosis or in those who have already formed a blood clot which needs treatment. This can prevent formation of blood clots and reduce the risk of embolism (spread) of a thrombus. Common indications for warfarin use are atrial fibrillation, artificial heart valves, deep venous thrombosis and pulmonary embolism.

Dosing of warfarin is complicated by the fact that it is known to interact with many commonly used medications and other chemicals which may be present in appreciable quantities in food. These interactions may enhance or reduce warfarin's anticoagulation effect. Many commonly used antibiotics such as metronidazole or the macrolides, will greatly increase the warfarin effect by reducing the metabolism of warfarin in the body. Other broad spectrum antibiotics can reduce the amount of the normal bacterial flora in the bowel which make significant quantities of Vitamin K, thus potentiating the effect of warfarin. In addition, food which contains large quantities of Vitamin K will reduce the warfarin effect and medical conditions such as hypo- or hyperthyroidism will alter the rate of breakdown of the clotting factors.

Therefore, in order to optimise the therapeutic effect without risking dangerous side effects such as bleeding, close monitoring of the degree of anticoagulation is required by blood testing (INR) . Initially, checking may be as often as twice a week; the intervals can be lengthened if the patient manages stable therapeutic INR levels on an unchanged warfarin dose.

When initiating warfarin therapy ("warfarinisation"), the doctor will decide how strong the anticoagulant therapy needs to be. A common target INR level is 2.0-3.0, though it varies from case to case.

The new oral anticoagulant ximelagatran (Exanta) does not require INR monitoring, and was expected to replace warfarin to a large degree when introduced; however, it has run into approval problems and as of 2005 it was not clear if or when it will ever become available for general use.

Pesticide use
Warfarin is used as a rodenticide for controlling rats and mice in residential, industrial, and agricultural areas. It is both odorless and tasteless. It is effective when mixed with food bait, because the rodents will return to the bait and continue to feed over a period of days, until a lethal dose is accumulated (considered to be 1 mg/Kg/day over four to five days). It may also be mixed with talc and used as a tracking powder, which accumulates on the animal's skin and fur, and is subsequently consumed during grooming. The use as rat poison is now declining because many rat populations have developed resistance to warfarin

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